Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
7/19/2012
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Have We Evolved The Metabolic Reserve To Survive Critical Injury and Illness?
Paul Wischmeyer M.D.
Associate Chair, Clinical and Translational
Research
Director, Nutrition Therapy Service, UCH
Director, Translational Pharmacology and
PharmacoNutrition Laboratory
Professor of Anesthesiology
University of Colorado SOM
© 2012 Abbott Laboratories
1
NIH FundingNIDDK- GLND TrialNIGMS- RO1GM078312 NHLBI- TOP-UP Trial
CIHR FundingREDOXS Trial, RE-ENERGIZE Trial
Dept. of Defense/ABA FundingRE-ENERGIZE Trial
Industry Financial Relationships:Occasional Consultant and Speaker:
Abbott, Baxter, Fresenius
DisclosuresDisclosures
2 2
Goals for LectureGoals for LectureUnderstand and describe the
hypermetabolic response to critical illness
Describe how hypermetabolic
3
Describe how hypermetabolic response effects substrate utilization
•How to utilize our understanding of the stress response to plan nutrition therapy (both EN and PN)
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“Survival For A Lifetime”
5 5
Optimizing Metabolic
Response For Our P ti t ?
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Patients?
Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
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MetabolismMetabolismin Acute in Acute IllnessIllness
77
XXX
X
1. Increased resting energy expenditure
2. Stress hormones limit lipolysis; stimulate lean body mass catabolism
Pathophysiologic Changes in Hypermetabolic Stress
8
XX
3. Fuel produced via hepatic gluconeogenesis
Wolfe RR. Circ Shock 1981;8:105-115.
9
Energy Expenditure of Organs
Organ% of Resting Metabolic
Rate
Liver 29 (Lipid)
Brain 19 (Glucose)
10
Skeletal muscle 18 (Lipid)
Heart 10 (Lipid)
Kidney 7 (Glucose)
Remainder (ie. bone, fat)
17
Chp 9, Energy balance, body composition… In Insel P et al (eds), Nutrition, 4th ed, Jones and Bartlett Publishers, Boston, 2011, Pg 342
10
Lipid is Preferred Fuel for MOST
Organs!
11
Organs!
Chp 7, Metabolism. In Insel P et al (eds), Nutrition, Jones & Bartlett Publishing, Boston, 2011, pg 298
11
HypermetabolismHypermetabolism
1212
Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
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Most calories from fat (Insulin Resistant!)Most calories from fat (Insulin Resistant!)
Minimal carbohydrate needed for CNS, blood, Minimal carbohydrate needed for CNS, blood, wound, kidneywound, kidney
Metabolism In Critical IllnessMetabolism In Critical Illness
13Wiener M et al, Critical Care Clinics 1987; 3: 25Wiener M et al, Critical Care Clinics 1987; 3: 25
Limited capacity to oxidize Limited capacity to oxidize glucose!glucose!
13
Carbohydrate/Lipid Oxidation in Sepsis
14
In septic patients and patients post-injury:
Fat!(rather than carbohydrate) is main substrate
Stoner HB: The effect of sepsis on the oxidation of carbohydrate and fat. Br J Surg 1983; 70: 32
Body Challenged To Use Glucose in
Critical Illness!
15
XXX
X
1. Increased resting energy expenditure
2. Stress hormones limit lipolysis; stimulate lean body mass catabolism
Pathophysiologic Changes in Hypermetabolic Stress
16
XX
3. Fuel produced via hepatic gluconeogenesis
4. Lean body mass is not preserved
Wolfe RR. Circ Shock 1981;8:105-115.
Hypermetabolic Stress Is Associated withLoss of Lean Body Mass
28
24
20
16on
(g
/day
) Severe Burn
Injury
Acute Sepsis
17Long CL, et al. JPEN J Parenter Enteral Nutr 1979;3:452-456.
16
12
8
4
0Nit
rog
en E
xcre
ti
p
Infection
Elective Surgery
Days0 10 20 30 40
Critically Ill Patients Can Lose As Much As 1 kg of Lean Body Mass Daily!
18
Loss of lean body mass accelerates in critical illness
Demling RH. Eplasty 2009;9:e9.
Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
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Metabolic Responses to Fasting and Hypermetabolic Stress
FastingHypermetabolic
Stress
Metabolic rate
19
Popp MB, Brennan MF. In: Fischer JF, ed. Surgical Nutrition.Boston, Little, Brown and Company, 1983:423-478.
Body fuels Conserved Wasted
Body protein Conserved Wasted
Urinary nitrogen
How do we Explain Hypermetabolism in How do we Explain Hypermetabolism in History of Mankind ??History of Mankind ??
20
21
How Do We Explain Nutrients Role in Illness and Injury?
Nutrients levels and lean body mass Nutrients levels and lean body mass is lost rapidlyis lost rapidly
Predicts ICU mortalityPredicts ICU mortality
Sh t t t f it l tSh t t t f it l t
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•• Short term stores of vital stress Short term stores of vital stress substrates and nutrientssubstrates and nutrients
• ER and ICU are recent developments
23 23 24
Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
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No ambulance coming...No ambulance coming...
Get well fastGet well fast or die......
How Do We Explain Nutrients Role in Illness and Injury?
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Get well fast Get well fast or die......
•• Thus…stores/balance of Thus…stores/balance of stress nutrients not stress nutrients not necessarynecessary
Now ambulance does rescue Now ambulance does rescue you..you..
I ICU k li fI ICU k li f
How Do We Explain Nutrients How Do We Explain Nutrients Role in Illness and Injury?Role in Illness and Injury?
26
In ICU we keep you alive for In ICU we keep you alive for months..months..
Now when underfed, you Now when underfed, you accumulate caloric debt and accumulate caloric debt and lose LBMlose LBM
Is that a problem? Is that a problem? 26
Must provide adequate Must provide adequate protein and calories toprotein and calories to
How Do We Explain Nutrients Role in Illness?
27
protein and calories to protein and calories to prevent loss of lean prevent loss of lean
body mass!body mass!
27
Loss of Lean Body Mass is Devastating
% Loss of Total LBM Complications
Associated Mortality (%)
10 Decreased immunity, increased infections
10
20 Decreased healing 30
28
20 Decreased healing, weakness, infection 30
30 Too weak to sit, pressure ulcers, pneumonia, no
healing
50
40 Death, usually from pneumonia 100
1970s - 1990s
Adjunctive care
2000 - today
Proactive therapeutic strategy
Evolution of Nutrition Therapy in Critical Care
Nutrition Support Nutrition Therapy
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• Preserve lean body mass
• Maintain immune function
• Avert metabolic complications
• Reduce disease severity
• Diminish complications
• Decrease intensive care unit length of stay
• Improve patient outcomes
McClave SA, et al. JPEN J Parenter Enteral Nutr 2009; 33:277-316.
Who Are Candidates for Nutrition Therapy?
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Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
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Prevalence of Malnutrition in Hospitalized Adults
30 50%
Hospital Malnutrition
31
30-50%Declines further with hospital stay
Green CJ. Clin Nutr 1999;18(s):3-28 31
Hospital Malnutrition
Weighted
32Clinical Nutrition 2008; 27: 5
Mean41.7%
32
Is malnutrition Is malnutrition related torelated to
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related to related to outcome?outcome?
Cumulative MortalityCumulative Mortalityrt
ality
rtal
ity
34
Months After HospitalizationMonths After HospitalizationAmerican Journal of Medicine (Cederholm T, Jägrén C, Hellström K. 1995;98:67-74). American Journal of Medicine (Cederholm T, Jägrén C, Hellström K. 1995;98:67-74).
% M
or%
Mor
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We Must Do Better!We Must Do Better!
35
But How??3636
Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
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ICU Nutrition GuidelinesICU Nutrition GuidelinesEarly EN (started at 24–48 h)
NG tube, EN feeding
EN before PN
37
Tolerate GRV 350-500
Promotility drugs if EN not tolerated
Small bowel feeding if NG feeding not tolerated
www.criticalcarenutrition.com 37
Right?...
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So.. everyone is So.. everyone is getting early and getting early and
successful enteral successful enteral feeding …feeding …
Right??Right??
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Right??Right??
NO !NO !
New York Hospital Association Survey
43%
40
of patients were
NPO on survey day
International Critical Care Nutrition Survey
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Deliver ~50% of prescribed Kcals/day
f ICU t !
We All Underfeed!
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for ICU stay!
Takes > 60 h to start feeding in ICU!
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Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
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Why Do We Why Do We Underfeed?Underfeed?
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Where Do Most Where Do Most Physicians Get Physicians Get
All Their All Their
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Nutrition Nutrition Education?Education?
45 4646
Critically Ill Patients Can Lose As Much As 1 kg of Lean Body Mass Daily!
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Loss of lean body mass accelerates in critical illness
Demling RH. Eplasty 2009;9:e9.
But...Pts who leave “my ICU” get better
and live healthy lives...
48
RIGHT?!?!
Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
7/19/2012
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What is the outcome of our ICU patients...
49
After they Leave the ICU?
Continued Effect of Sepsis on Survival
50Quartin et al. JAMA 1997; 277:1058-1063
Survival after severe sepsis
51Weycker, et al. CCM 2003
> 40%of Mortality at 6/12
52
Month Follow-up Occurs
Post-ICU Discharge
Shiell AM, Griffiths RD et al Clinical Intensive Care 1990;1 (6): 256-262
Surviving patients recover pre-
illness function
53
eventually....Right??
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Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
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3 mon
6 mon
6 Minute Walking Distance (Median) Predicted Value
Exercise Ability Following ICU DischargeExercise Ability Following ICU Discharge
49% Predicted!
64% Predicted!
55
0 200 400 600 800
6 mon
12 mon 66% Predicted!
Meters Walked in 6 MinutesMeters Walked in 6 Minutes 55
Physical Role Score (SF-36) Following ICU Discharge
Physical Role Score (SF-36) Following ICU Discharge
60
80
100
Physical Role Score (Med) Normal Value
56
0 0 250
20
40
60
3 months 6 months 12 months
56
But... this must improve after 12
months
57
months....Right??
NO!Exercise Limitation
and Reduced Physical Fxn
58
PERSISTS
5-YEARS
post-ICU
Why ?Why ?
59
Weight change from pre-ICU status
60Herridge et al. NEJM 2003;348:683-693
Not Lean Mass Gain!.. Mostly Fat!
Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
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Loss of Lean Body Mass is Devastating
% Loss of Total LBM Complications
Associated Mortality (%)
10 Decreased immunity, increased infections
10
61
20 Decreased healing, weakness, infection 30
30 Too weak to sit, pressure ulcers, pneumonia, no
healing
50
40 Death, usually from pneumonia 100
6262
How Do We Assess Nutritional Status in the ICU?
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Nutritional AssessmentNutritional AssessmentBiochemical analysisBiochemical analysis
There is NO gold standard marker!
64
standard marker!
All Serum Markers (Albumin, Pre-Albumin, Transferrin)
have poor reliability64
Levels are decreased in critically ill patients
Visceral Proteins Indicate Metabolic Status Rather Than Nutritional Status
Alb i
Acute phase proteins
( C ti
65
Transcapillary protein lossesHepatic synthesis reprioritized
AlbuminPrealbuminTransferrin
(eg, C-reactive protein)
Jensen GL. JPEN J Parenter Enteral Nutr 2006;30:453-463.
Nutritional AssessmentNutritional AssessmentBiochemical analysisBiochemical analysis
If CRP < 5 the Pre-Albumin is better marker
66
better marker
If CRP > 5 patient will not be anabolic and Pre-ALB is pretty
useless!
66
Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
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Nutritional AssessmentNutritional AssessmentBiochemical analysisBiochemical analysis
If CRP > 5 we have to
67
If CRP > 5 we have to figure out why...
And fix it!!!
What Happens When Adequate Nutrition Is Not
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Given?
What About PN?
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Patients need different goals…Patients need different goals…
How do we decide?How do we decide?
Caloric Intake in Critical IllnessCaloric Intake in Critical Illness
70
BMI??BMI??
70
International Critical Care Nutrition Survey
71
HypothesisHypothesis
Relationship of energy/protein to Relationship of energy/protein to clinical outcome clinical outcome (mortality!)(mortality!)
Relationship influenced by Relationship influenced by
72
nutritional risknutritional risk
BMI defines chronic nutritional riskBMI defines chronic nutritional risk
72
Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
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40 0000
50.0000
60.0000
70.0000
All Patients < 20 20-25 25-30 30-35 35-40 > 40
Relationship of Caloric Intake, 60 day Mortality and BMI
0.0000
10.0000
20.0000
30.0000
40.0000
0 500 1000 1500 2000
Alberda,C, Heyland D et alIntensive Care Med.35:1728-37. 2009 74
Extra-Protein Reduces Mortality as well..
74
Every additional 30 grams/d protein given...
Mortality decreased!
Effect of Increasing Protein on Infection
Multicenter observational study- 207 pts >72 h in ICU
75
For increase of 30 g/d:OR of infection at 28 dHeyland Clinical Nutrition 2011
(REDOXS Study)First 364 pts w/ SF-36 Score at 3 m and/or 6 m
Model *Estimate (CI) P values
(B) Increased protein intake
PHYSICAL FUNCTIONING (PF) at 3 months 2.9 (-0.7, 6.6) P=0.11
Increased Protein Intake Improves Physical Function Post-ICU
76
for increase of 30 gram/day, OR of infection at 28 days
Heyland Unpublished Data
S C UNC ON NG ( ) at 3 o t s .9 ( 0.7, 6.6) 0.
ROLE PHYSICAL (RP) at 3 months 4.4 (0.7, 8.1) P=0.02
STANDARDIZED PHYSICAL COMPONENT SCALE (PCS) at 3 months
1.9 (0.5, 3.2) P=0.007
PHYSICAL FUNCTIONING (PF) at 6 months 0.2 (-3.9, 4.3) P=0.92
ROLE PHYSICAL (RP) at 6 months 1.7 (-2.5, 5.9) P=0.43
STANDARDIZED PHYSICAL COMPONENT SCALE (PCS) at 6 months
0.7 (-0.9, 2.2) P=0.39
Has this already been shown in a
multi-center RCT?
77 7878
Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
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0
7979 8080
Why?Why?
81 8282
Did 5 x protein Did 5 x protein save lives?save lives?
83
EDEN Trial Increased Energy Delivery Improves Discharge Home vs. Rehab Center
*
84
Full-Energy
* - p < 0.04 vs Trophic Feeding Rice et al. Crit Care Med 39, 201184
Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
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Optimal Protein and Energy Nutrition Decreases Mortality in Mechanically Ventilated, Critically Ill Patients: A Prospective
Observation Cohort StudyWeijs PJM et al. JPEN, 2012;36(1):60-68
886 MV ICU pts predicted to need artificial nutrition for > 7-10 days
Calories via metabolic cart: min. protein goal- 1.2 gr/kg/d
• Energy/Protein Intake Recorded for MV Period
85
Groups:
- No Target reached:
Neither protein or energy targets achieved during MV period- 412 pts
- Protein + Energy Target reached - 245 pts
- Energy Target reached- 205 pts
No differences in:
Apache, Age, Diagnosis Type by Group 85
Results: Protein Delivery Mean
Optimal Protein and Energy Nutrition Decreases Mortality in Mechanically Ventilated, Critically Ill Patients: A Prospective
Observation Cohort StudyWeijs PJM et al. JPEN, 2012;36(1):60-68
- No Target Achieved: 0.83 g/kg/d
- Energy Target Only: 1.06 g/kg/d
- Protein/Energy Target: 1.31 g/kg/d
86
Achieving Protein/Energy Goals Reduces Risk of Death in High Mortality Risk ICU Patients
PET- Reached Protein/Energy TargetsET- Reached Energy Targets Only
UnadjustedAdjusted for sex, age, BMI, diag.,
hyperglycemic index, and APACHE II
Adjusted for PN Use and Time to Goal Nutrition
87Weijs PJM et al. JPEN, 2012;36(1):60-68
When EN is When EN is not Enough...not Enough...
…Should I Start …Should I Start PN??PN??
88
PN??PN??
88
If EN not feasible in first 7 d in ICU no specialized nutrition therapy should be initiated (C)
SCCM / ASPEN Guidelines 2009SCCM / ASPEN Guidelines 2009PN Guidelines PN Guidelines
89
Patients previously healthy 7 d (E)
Patients with evidence of malnutrition start ASAP (C)
89
ESPEN Guidelines 2009ESPEN Guidelines 2009PN Guidelines PN Guidelines
ALL PATIENTS not expected to be on normal nutrition within 3 d should receive PN w/in 24 to 48 h if no EN contraindicated or not
90
if no EN contraindicated or not tolerated (C)
• ALL PATIENTS receiving less than target EN after 2 d should be considered for supplementary PN. (C)
Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
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They Sound Different
91
Different...
But..
Both advocate Early PN
for
92
for malnourished
patients..
Aren’t There Aren’t There Some New Trials Some New Trials
in PN?in PN?
93
Comparison of Recent and Comparison of Recent and Planned SPN TrialsPlanned SPN Trials
94
Study-1.1-1.2 g/kg/d
What Else Can We Learn From The Differences in These Trials?
95
These Trials?
96
Study-1.1-1.2 g/kg/d
Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
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Keys Factors to Make PN
97
Decisions!
98
99Mortality Risk 99 100
Protein Delivery(1.2-2.0 g/kg/day)
101101
When to consider PNWhen to consider PNPN only after EN and motility agent
Must Deliver 1.2-2.0 g/kg/d Protein
In High Mortality Risk Patients!
102
ote
Well nourished (BMI 25-35)
After no EN for 7
Malnourished (BMI <25, >35)
If EN not at goal in 48-72 h
Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
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In Summary...In Summary...
103
Key ConceptsKey ConceptsFuel use is effected by
hypermetabolic stress
All critically ill pts are candidates for nutrition therapy (with EN and/or PN)
104
Key to provide adequate protein delivery to optimize LBM preservation
Nutrition delivery may be vital to optimizing long term ICU outcome
Have We Evolved The Metabolic Reserve To Survive Critical Injury and Illness?
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Not Without Help From You!
106
We Can Help Our Patients Evolved
Survival
107
Survival Mechanisms Via
Nutrition!
Just Do It...
108 108
Have We Evolved the Metabolic Reserve to Survive Critical Injury and Illness?
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Alberda C, Gramlich L, Jones N, Jeejeebhoy K, Day AG, Dhaliwal R, Heyland DK. The relationship between nutritional intake and clinical outcomes in critically ill patients: results of an international multicenter observational study. Intensive Care Med. 2009; 35(10):1728-37.
Cederholm T, Jägrén C, Hellström K. Outcome of protein-energy malnutrition in elderly medical patients. Am J Med. 1995;98(1):67-74.
Demling RH. Nutrition, anabolism, and the wound healing process: an overview. Eplasty. 2009;9:e9.
Green CJ. Existence causes and consequences of disease related malnutrition in the hospital and the community, and the clinical and financial benefits of nutritional intervention. Clin Nutr 1999;19(Suppl 2):3S-38S.
Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, Stewart TE, Barr A, Cook D, Slutsky AS; Canadian Critical Care Trials Group. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med. 2003;348(8):683-93.
References
109
Heyland DK, Stephens KE, Day AG, McClave SA. The success of enteral nutrition and ICU-acquired infections: a multicenter observational study. Clin Nutr. 2011;30(2):148-55.
Jensen GL. Inflammation as the key interface of the medical and nutrition universes: a provocative examination of the future of clinical nutrition and medicine. JPEN J Parenter Enteral Nutr. 2006;30(5):453-63.
Long CL, Schaffel N, Geiger JW, Schiller WR, Blakemore WS. Metabolic response to injury and illness: estimation of energy andprotein needs from indirect calorimetry and nitrogen balance. JPEN J Parenter Enteral Nutr. 1979;3(6):452-6.
McClave SA, Martindale RG, Vanek VW, McCarthy M, Roberts P, Taylor B, Ochoa JB, Napolitano L, Cresci G; A.S.P.E.N. Board of Directors; American College of Critical Care Medicine; Society of Critical Care Medicine. Guidelines for the Provision andAssessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr. 2009;33(3):277-316.
109
Norman K, Pichard C, Lochs H, Pirlich M. Prognostic impact of disease-related malnutrition. Clin Nutr. 2008;27(1):5-15.
Quartin AA, Schein RM, Kett DH, Peduzzi PN. Magnitude and duration of the effect of sepsis on survival. Department of Veterans Affairs Systemic Sepsis Cooperative Studies Group. JAMA. 1997;277(13):1058-63.
Rice TW, Mogan S, Hays MA, Bernard GR, Jensen GL, Wheeler AP. Randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure. Crit Care Med. 2011;39(5):967-74.
Shiell AM, Griffiths RD, Short AI, Spiby J. An evaluation of the costs and outcome of adult intensive care in two units in the UK. Clin Intensive Care. 1990;1(6):256-62.
Stoner HB, Little RA, Frayn KN, Elebute AE, Tresadern J, Gross E. The effect of sepsis on the oxidation of carbohydrate and fat.Br J Surg. 1983;70(1):32-5.
Weijs PJ, Stapel SN, de Groot SD, Driessen RH, de Jong E, Girbes AR, Strack van Schijndel RJ, Beishuizen A. Optimal protein and energy nutrition decreases mortality in mechanically ventilated, critically ill patients: a prospective observational cohort
References
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study.JPEN J Parenter Enteral Nutr. 2012;36(1):60-8.
Weycker D, Akhras KS, Edelsberg J, Angus DC, Oster G. Long-term mortality and medical care charges in patients with severe sepsis. Crit Care Med. 2003;31(9):2316-23.
Wiener M, Rothkopf MM, Rothkopf G, Askanazi J. Fat metabolism in injury and stress. Crit Care Clin. 1987;3(1):25-56.
Wolfe RR. Review: acute versus chronic response to burn injury. Circ Shock. 1981;8(1):105-15.